Slc11a1-KO Mouse

Slc11a1, also known as NRAMP1 (Natural resistance associated macrophage protein 1), encodes a phagosomal membrane protein located in monocytes. It functions as a metal ion transporter, playing a role in innate immunity by restricting pathogen growth, and is associated with autoimmune diseases and infections [1,2,4,6].

In mice, Slc11a1 deficiency impairs Salmonella control as immature neutrophils with reduced Slc11a1 expression fail to restrict pathogen growth, and adoptive transfer of SLC11A1-proficient neutrophils can reduce systemic Salmonella burden in Slc11a1 -/- mice or those with vitamin A deficiency [6]. Polymorphisms in SLC11A1 are associated with increased susceptibility to tuberculosis in humans, and its down-regulation in TB patients may impair the immunological response [1,7].

In cancer, SLC11A1 is highly expressed in glioma, kidney renal clear cell carcinoma (KIRC), and colorectal cancer (CRC), predicting unfavorable prognosis. In KIRC, SLC11A1 promotes tumor progression by remodeling the tumor microenvironment, while in CRC, it is associated with more macrophage and fibroblast infiltration in the tumor microenvironment, and higher SLC11A1 levels are related to fewer immunotherapy benefits [3,4,5,9].

In a murine model of ulcerative colitis, the Slc11a1 S allele makes mice more susceptible to DSS-induced colitis [8].

In conclusion, Slc11a1 is crucial for innate immunity, especially in pathogen control. Its deficiency or polymorphisms are linked to increased susceptibility to infections like tuberculosis and Salmonella. In cancer, its high expression is often associated with poor prognosis and impacts the tumor microenvironment and immunotherapy response. Mouse models, including gene-knockout models, have been instrumental in revealing its role in these biological processes and disease conditions.